Pachyonychia congenita

[Anonymous]

Pachyonychia congenita (PC) is a group of autosomal dominantly inhereited disease characterized by dystrophic nail, palmoplantar hyperkeratosis, accompanied by varying features of ectodermal dysplasia. It is a rare genodermatosis, usually inherited as an autosomal dominant trait with varying degree of penetrance. PC is characterized by the marked subungual hyperkeratosis with thickening of the distal part of the nails. The other findings includes palmer and plantar keratosis, hyperhydrosis, follicular hyperkeratosis and frequent blistering of the feet. The oral manifestations in PC includes luekokeratosis of tongue, leukoplakia, pilosebaceous cyst, neonatal teeth, angular chelitis, and laryngeal involvement leading to the hoarseness of voice. Leukokeratosis of oral mucosa is a predominant feature of PC which mainly occurs on tongue, buccal mucosa, and some times on gingiva. PC was first described by Muller and Wilsen in 1904, but it was Jadassohn Lewandowsky in 1906 who reported anomaly of nail, palmoplantar keratoderma, ectodermal defects and gave the name PC.
The manifestation of PC are chiefly subungual hyperkeratosis with marked thickening of the distal portions of the nails and severe disabling hyperkeratosis of the palms and soles. The thickening results from the subungual hyperkeratosis with an upward angulation of the distal portion of the nail tip. The dorsal surface of the nail is smooth, where as lateral borders often curve toward the center in pinched manner. Other manifestations include follicular hyperkeratosis, observed on face and on the extensor aspect of the proximal parts of the extremities, hyperhidrosis, particularly on palms and soles, corneal changes, and epideramal inclusion cysts.
PC usually begins in infancy, but late onset PC, referred to as pachyonychia congenita tarda, which begins in the fourth or fifth decade, has also been reported. It frequently affects Jewish and Yugoslavian race with female predominance.

        

[Anonymous]

The oral rehabilitation of patients affected by PC should be directed to eliminate the possibility of chronic trauma to the oral mucosa. Despite the importance of oral rehabilitation, there are no reports of prosthetic devices for these patients. The edges of the prosthesis and the cusps of the teeth were constructed to be of uniform thickness and rounded to avoid any further trauma to the tissues.

        

[sushantpatel_doc]

Disease characteristics
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, focal palmoplantar keratoderma and blistering, oral leukokeratosis, cyst formation, palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities. PC includes two main subtypes, pachyonychia congenita type 1 (PC-1) and pachyonychia congenita type 2 (PC-2). Variants of PC include focal non-epidermolytic palmoplantar keratoderma (FNEPPK), with keratoderma occurring on the palms and soles but usually without nail dystrophy; steatocystoma multiplex (SM) with widespread cysts but with little or no nail involvement or palmoplantar keratoderma; and late-onset PC (PC tarda), which resembles either PC-1 or PC-2 and has onset from late childhood to middle age.

Diagnosis/testing
PC is diagnosed by clinical findings and by molecular genetic testing. The two keratin genes known to be associated with PC-1 are KRT6A (encoding keratin, type II cytoskeletal 6a) and KRT16 (encoding keratin, type I cytoskeletal 16). The two keratin genes known to be associated with PC-2 are KRT6B (encoding keratin, type II cytoskeletal 6b) and KRT17 (encoding keratin, type I cytoskeletal 17). Molecular genetic testing of these four genes is available on a clinical basis.

Management
Treatment of manifestations: Pain from the palmoplantar keratoderma can be reduced by limiting friction and trauma to the feet by minimizing walking or standing, reducing hydration of the stratum corneum by using wicking socks and ventilated footwear, selecting comfortable shoes, and maintaining ideal body weight. Foot care includes paring down hyperkeratotic areas and topical therapies for hyperkeratosis including emollients and lotions containing keratolyics. Early detection permits treatment of secondary bacterial and yeast/fungal infections on the feet and nails and in the mouth. Care of thickened nails often requires the use of surgical or razor blades or sanders such as a Dremel® tool. Troublesome nails can be removed surgically. Frequent brushing of teeth can improve the appearance of thick, white patches on the tongue and oral mucosa. Poor feeding in infants with leukokeratosis may require use of a bottle with a soft nipple and an enlarged opening. Rarely, emergency surgical intervention may be needed to re-establish the airway in young children with laryngeal thickening/growths. Steatocystoma multiplex and other pilosebaceous cysts can be treated initially by incision and drainage. Prevention of secondary complications: attention to pre- and post-grooming hygiene to prevent infection. Agents/circumstances to avoid: trauma, friction, and sheer forces to the skin and nails. Therapies under investigation: Studies on the use of a K6a mutation-specific siRNA, rapamycin, anti-TNF biologics, and botulism toxin are underway.

Genetic counseling
Pachyonychia congenita is inherited in an autosomal dominant manner. Approximately 50% of cases appear to result from a de novo mutation. Offspring of an affected individual have a 50% chance of inheriting the disorder. Prenatal diagnosis is possible for pregnancies at increased risk if the disease-causing mutation in the family is known.

        

[sushantpatel_doc]

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